LIFEHOUSE's Functional Nutrition Examination (Physical Exam, Anthropometrics, and Selected Biomarkers) Informs Personalized Wellness Interventions.

Each individual has a unique and interacting set of genetic, lifestyle, and environmental factors that are reflected in their physical exam and laboratory biomarkers and significantly impact their experience of health. Patterns of nutrient deficiency signs and biomarker levels below health-promoting thresholds have been identified in national nutrition surveys. However, identifying these patterns remains a challenge in clinical medicine for many reasons, including clinician training and education, clinical time restraints, and the belief that these signs are both rare and recognizable only in cases of severe nutritional deficiencies. With an increased interest in prevention and limited resources for comprehensive diagnostic evaluations, a functional nutrition evaluation may augment patient-centered screening evaluations and personalized wellness programs. During LIFEHOUSE, we have documented physical exam, anthropometric, and biomarker findings that may increase the recognition of these wellness-challenging patterns in a population of 369 adult employees working in two occupational areas: administrative/sales and manufacturing/warehouse. Distinct and significant physical exam differences and constellations of biomarker abnormalities were identified. We present these patterns of physical exam findings, anthropometrics, and advanced biomarkers to assist clinicians in diagnostic and therapeutic interventions that may stem the loss of function that precedes the development of the non-communicable chronic diseases of aging.

The gastrointestinal and microbiome impact of a resistant starch blend from potato, banana, and apple fibers: A randomized clinical trial using smart caps.

The gastrointestinal (GI) impact of fibers including resistant starch (RS) consumption depends on various types and amounts of fibers, the initial microbiome states, and accurate intake measurements. A randomized clinical trial evaluated the GI impact of varying doses of a novel resistant starch blend (RSB) with smart cap monitoring. RSB contained at least 50% RS and was a proprietary mixture of a potato starch, green banana flour, and apple fiber powder (a source of apple pectin, not resistant starch). The study design randomized participants to one of four arms: 10 g/day of potato starch (0 RSB), 10 g/day of RSB, 10 to 20 to 20 g/day of RSB or 10 to 20 to 30 g/day RSB for two-week intervals over 6 weeks. Results confirmed that while resistant starch of approximately 5 g per day improves GI symptoms at 2, 4, and 6 weeks, it did not demonstrate a detectable effect on short chain fatty acids. Increasing doses of the blend (RSB) led to a decrease in the diarrhea score. Using an estimate of total consumption of RSB based on smart cap recordings of container openings and protocol-specified doses of RSB, a reduction in the sleep disturbance score was associated with higher RSB dose. The exploratory microbiome evaluation demonstrated that among the 16S rRNA gene sequences most associated with the consumption of the novel blend RSB, two belong to taxa of notable interest to human health: Faecalibacterium and Akkermansia.

Our Healing Journey: Restoring Connection, Finding Hope and Evolving Wellness.

Wellness is more than the simple absence of disease. As such, health can be envisioned as a journey to a state of optimal wellness and not a simple destination. To measure progress on such a journey, defining wellness by measures other than disease risk factors and biomarkers is necessary. Health can be defined by five areas of functionality: metabolic, physical, emotional, cognitive, and behavioral. Indeed, an individual's behaviors are the outward expression of an inward integration of the metabolic, physical, emotional, and cognitive functions in a fully actualized mind, body, and spirit. Personalized Lifestyle Medicine recognizes the importance of facilitating lasting behavioral change but facilitating this change may be difficult and may resist standard practice models. It is our proposal that a major obstacle on the journey to achieving full wellness is the brokenness of an individual's connections to self, to purpose, to community, and to the environment. Programs aimed both at defining an individual's authentic self and providing patient education using Functional Medicine's unique philosophy can facilitate a patient's creation of a lasting vision that is the work of successful behavioral change.

Genetic Biomarkers of Metabolic Detoxification for Personalized Lifestyle Medicine.

Metabolic detoxification (detox)-or biotransformation-is a physiological function that removes toxic substances from our body. Genetic variability and dietary factors may affect the function of detox enzymes, thus impacting the body's sensitivity to toxic substances of endogenous and exogenous origin. From a genetic perspective, most of the current knowledge relies on observational studies in humans or experimental models in vivo and in vitro, with very limited proof of causality and clinical value. This review provides health practitioners with a list of single nucleotide polymorphisms (SNPs) located within genes involved in Phase I and Phase II detoxification reactions, for which evidence of clinical utility does exist. We have selected these SNPs based on their association with interindividual variability of detox metabolism in response to certain nutrients in the context of human clinical trials. In order to facilitate clinical interpretation and usage of these SNPs, we provide, for each of them, a strength of evidence score based on recent guidelines for genotype-based dietary advice. We also present the association of these SNPs with functional biomarkers of detox metabolism in a pragmatic clinical trial, the LIFEHOUSE study.

Personalized Lifestyle Intervention and Functional Evaluation Health Outcomes SurvEy: Presentation of the LIFEHOUSE Study Using N-of-One Tent-Umbrella-Bucket Design.

The working definition of health is often the simple absence of diagnosed disease. This common standard is limiting given that changes in functional health status represent early warning signs of impending health declines. Longitudinal assessment of functional health status may foster prevention of disease occurrence and modify disease progression. The LIFEHOUSE (Lifestyle Intervention and Functional Evaluation-Health Outcomes SurvEy) longitudinal research project explores the impact of personalized lifestyle medicine approaches on functional health determinants. Utilizing an adaptive tent-umbrella-bucket design, the LIFEHOUSE study follows the functional health outcomes of adult participants recruited from a self-insured employee population. Participants were each allocated to the tent of an all-inclusive N-of-one case series. After assessing medical history, nutritional physical exam, baseline functional status (utilizing validated tools to measure metabolic, physical, cognitive, emotional and behavioral functional capacity), serum biomarkers, and genomic and microbiome markers, participants were assigned to applicable umbrellas and buckets. Personalized health programs were developed and implemented using systems biology formalism and functional medicine clinical approaches. The comprehensive database (currently 369 analyzable participants) will yield novel interdisciplinary big-health data and facilitate topological analyses focusing on the interactome among each participant's genomics, microbiome, diet, lifestyle and environment.

Spatially Resolved Molecular Compositions of Insoluble Multilayer Deposits Responsible for Increased Pollution from Internal Combustion Engines.

Internal combustion engines are used heavily in diverse applications worldwide. Achieving the most efficient operation is key to improving air quality as society moves to a decarbonized energy system. Insoluble deposits that form within internal combustion engine components including fuel injectors and filters negatively impact CO2 and pollutant emissions. Understanding the composition, origins, and formation mechanisms of these complex materials will be key to their mitigation however, previous attempts only afforded nondiagnostic chemical assignments and limited knowledge toward this. Here, we uncover the identity and spatial distribution of molecular species from a gasoline direct injector, diesel injector, and filter deposit in situ using a new hyphenation of secondary ion mass spectrometry and the state-of-the-art Orbitrap mass analyzer (3D OrbiSIMS) and elemental analysis. Through a high mass resolving power and tandem MS we unambiguously uncovered the identity, distribution, and origin of species including alkylbenzyl sulfonates and provide evidence of deposit formation mechanisms including formation of longer chain sulfonates at the gasoline deposit's surface as well as aromatization to form polycyclic aromatic hydrocarbons up to C66H20, which were prevalent in the lower depth of this deposit. Inorganic salts contributed significantly to the diesel injector deposit throughout its depth, suggesting contamination over multiple fueling cycles. Findings will enable several strategies to mitigate these insoluble materials such as implementing stricter worldwide fuel specifications, modifying additives with adverse reactivity, and synthesizing new fuel additives to solubilize deposits in the engine, thereby leading to less polluting vehicles.

A Low-Glycemic, Mediterranean Diet and Lifestyle Modification Program with Targeted Nutraceuticals Reduces Body Weight, Improves Cardiometabolic Variables and Longevity Biomarkers in Overweight Subjects: A 13-Week Observational Trial.

Among the comorbidities of high body mass index, cardiovascular disease continued to be the leading cause of death and disability globally in 2015, while type 2 diabetes remained second. The primary objectives of this observational study were to confirm the safety, tolerability, and efficacy of our calorie-restricted Mediterranean diet with targeted dietary supplementation (PROG1) using globally recognized dietary supplementation. Fifty healthy overweight and obese subjects with cardiometabolic risk factors were assigned a modified Mediterranean diet, including protein shakes and targeted supplementation (PROG2), providing ∼68-76% of subject estimated calorie requirements. Salivary nitrite was assessed weekly and key cardiometabolic metrics were recorded at baseline and weeks 9 and 13. PROG2 was well tolerated with 86% compliance. The most common adverse effects were bloating, flatulence, and constipation, which were self-limiting. Subjects exhibited decreases (P < .01) from baseline of 12% in body weight, 18% in body fat, and 8.8% in waist circumference. Total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, and triglycerides (TG) were reduced (P < .01), respectively, 19%, 22%, and 40%. Lipid ratios of TC/high-density lipoprotein (HDL), TG/HDL, and oxidized LDL (oxLDL)/HDL were decreased 15% (P < .01), 35% (P < .01), and 13% (P < .05), respectively. Inflammation biomarkers, oxLDL and high-sensitivity C-reactive protein, were reduced 17% (P < .01) and 30% (P < .05), respectively. Reductions of 9.0% for systolic (P < .01) and 12% (P < .01) for diastolic blood pressure were noted. In concert, the nitrogen dioxide salivary biomarker for nitric oxide was increased relative to baseline. PROG2 produced a dramatic 50% reduction in subjects meeting cardiometabolic syndrome criteria and a 38% decrease in Framingham 10-year cardiovascular risk. These results confirmed our previous findings that the addition of targeted nutraceutical supplementation to a calorie-restricted Mediterranean diet with lifestyle modifications improves multiple longevity risk factors more effectively than diet and lifestyle modification alone.

A 13-week low glycemic load diet and lifestyle modification program combining low glycemic load protein shakes and targeted nutraceuticals improved weight loss and cardio-metabolic risk factors.

An open-label, randomized, exploratory study of 44 healthy overweight subjects with cardio-metabolic syndrome (CMS) risk factors was conducted to assess the safety, tolerability, and efficacy of a proprietary lifestyle modification program without (DIET) and with (PROG) targeted nutraceutical supplementation, including phytosterols, antioxidants, probiotics, fish oil, berberine, and soy, pea, and whey proteins over 13 weeks. Key metrics were recorded at baseline and weeks 9 and 13. For the DIET and PROG groups, compliance was 85% and 86%, respectively, with no adverse events related to the diet or supplements. Twelve subjects discontinued participation before week 9 for reasons unrelated to the study. PROG subjects experienced greater decreases (p < 0.05) than DIET in body mass, fat mass, total cholesterol, LDL cholesterol, TG, cholesterol / HDL ratio, TG/HDL ratio, apolipoprotein B / apolipoprotein A1 ratio, and hs-CRP. The Framingham 10-year cardiovascular disease risk score decreased by 40% (p < 0.01) in the PROG arm versus no change for the DIET arm. As a pilot study, it was not possible to state whether the observed effects were the result of nutraceutical supplementation alone or the result of additive or synergistic interactions among diet, lifestyle modifications, and nutraceutical supplementation. Moreover, individuals with CMS risk factors following a lifestyle modification program received additional health benefits from targeted nutraceutical supplementation.

Synergistic in vitro antioxidant activity and observational clinical trial of F105, a phytochemical formulation including Citrus bergamia, in subjects with moderate cardiometabolic risk factors.

We examined the clinical safety and efficacy of F105 in 11 subjects with moderate dyslipidemia. F105 is a combination of bergamot fruit extract (Citrus bergamia, BFE) and 9 phytoextracts selected for their ability to improve the antioxidant and anti-inflammatory activity of BFE. In vitro F105 exhibited a synergistic inhibition of oxygen radical absorbing capacity, peroxynitrite formation, and myeloperoxidase activity. Following 12 weeks of F105 daily, no treatment-related adverse events or changes in body mass were seen. Statistically significant changes were noted in total cholesterol (-7.3%), LDL-cholesterol (-10%), non-HDL cholesterol (-7.1%), cholesterol/HDL (-26%), and apolipoprotein B (-2.8%). A post hoc analysis of 8 subjects with HbA1c > 5.4 and HOMA-IR score > 2 or elevated triglycerides revealed additional statistically significant changes in addition to those previously observed in all subjects including triglycerides (-27%), oxLDL (-19%), LDL/HDL (-25%), triglycerides/HDL (-27%), oxLDL/HDL (-25%), and PAI-1 (-37%). A follow-up case report of a 70-year-old female patient, nonresponsive to statin therapy and placed on F105 daily, demonstrated improved cardiometabolic variables over 12 weeks similar to the subgroup. In summary, F105 was clinically well-tolerated and effective for ameliorating dyslipidemia in subjects with moderate cardiometabolic risk factors, particularly in the individuals with HbA1c > 5.4%.

A Phytochemical-rich Multivitamin-multimineral Supplement Is Bioavailable and Reduces Serum Oxidized Low-density Lipoprotein, Myeloperoxidase, and Plasminogen Activator Inhibitor-1 in a Four-week Pilot trial of Healthy Individuals.

BACKGROUND: A multivitamin-multimineral supplement combined with a diverse blend of bioactive phytochemicals may provide additional antioxidant capacity and anti-inflammatory property for overall health. This convenient feature may be useful for individuals who want to increase their intake of phytochemicals. METHODS: We conducted a pilot study in 15 healthy individuals (8 women and 7 men, mean age 41.7±14.9 years, mean body mass index 28.0±5.6) to investigate the effects of this novel formulation on biomarkers associated with oxidative stress and inflammation. After a 2-week diet that limited intake of fruits and vegetables to 2 servings/day, participants continued with the same restricted diet but began consuming 2 tablets of the study product for the subsequent 4 weeks. Fasting blood samples collected at Week 2 and Week 6 were analyzed and compared using paired t-tests for levels of carotenoids, folate, vitamin B12, homocysteine, oxidized low-density lipoprotein cholesterol (oxLDL), high-sensitivity C-reactive protein (hs-CRP), F2-isoprostane, plasminogen activator inhibitor-1 (PAI-1), and myeloperoxidase. Noninvasive peripheral arterial tonometry (EndoPAT) was also measured. RESULTS: After 4 weeks of supplementation, plasma levels of carotenoids, folate, and vitamin B12, but not homocysteine, were significantly increased (P<.05). Serum levels of oxLDL, PAI-1 and myeloperoxidase were significantly reduced (P<.05), but F2-isoprostane, hs-CRP, and EndoPAT measures were unchanged compared with baseline. The study product was well tolerated. CONCLUSIONS: This nutritional supplement is bioavailable as indicated by the significant increase in plasma carotenoids, vitamin B12, and folate levels and may provide health benefits by significantly reducing serum levels of oxLDL, myeloperoxidase, and PAI-1 in healthy individuals.

The Heart and Medicine: Exploring the Interconnectedness of Cardiometabolic-related Concerns Through a Systems Biology Approach.

Patients do not just wake up one morning with cardiac disease. Instead there is an extended preclinical phase during which lifestyle choices determine outcome. Recent advances in our understanding of oxidative stress, endocrine signaling, immune/inflammatory balance, and energy production illuminate opportunities for efficacious intervention. A thorough exploration of these pathophysiologies will allow physicians the opportunity to offer their patients a journey away from illness and disease to optimal wellness.

Los pacientes no se levantan de repente una mañana con una enfermedad coronaria. En cambio, existe una fase preclínica larga durante la cual la elección del estilo de vida determina los resultados. Los avances recientes en nuestro entendimiento sobre el estrés oxidativo, las señales endocrinas, el equilibrio inflamatorio/inmune y la producción energética abren las oportunidades para una intervención eficaz. Una exploración minuciosa de estas patofisiologías permitirá a los médicos ofrecer a los pacientes la oportunidad de un viaje lejos de su enfermedad hacia un bienestar óptimo.

The Effects of Tetrahydro-iso-alpha Acids and Niacin on Monocyte-Edothelial Cell Interactions and Flow-mediated Vasodilation.

Niacin favorably modifies cardiovascular risk factors but is associated with flushing and shows limited benefit in improving endothelial function. We investigated whether combining anti-inflammatory tetrahydro-iso-alpha acids (THIAA) from hops with niacin would improve endothelial function. We hypothesized that the THIAA+niacin combination would demonstrate benefits not seen with niacin alone. In an in vitro model, a THIAA+niacin mixture inhibited several TNF-α-induced cytokines in human aortic endothelial cells and in human monocytic cells and was significantly more efficacious than niacin alone. Subsequently, the effect of 125 mg THIAA and 500 mg niacin on endothelial-regulated flow-mediated vasodilation (FMD) was explored in a pilot study of 11 dyslipidemic volunteers. The 12-week treatment (2 tablets/day) resulted in a clinically relevant FMD increase compared to a trend toward an FMD decrease with placebo; the between-arm difference was statistically significant. THIAA+niacin treatment also improved total cholesterol, low-density lipoprotein cholesterol, and uric acid. No significant improvement in these parameters was observed with placebo. High-sensitivity C-reactive protein was significantly increased only in the placebo arm. Nutritional support with a THIAA+niacin combination may provide benefits for endothelial function in those with dyslipidemia.

La niacina modifica favorablemente los factores de riesgo cardiovascular pero se asocia con la rubefacción y presenta un beneficio escaso en la mejora de la función endotelial. Investigamos si la combinación de ácidos tetrahidro-iso-alfa (tetrahydro-iso-alpha acids, THIAA) de lúpulo antiinflamatorios con niacina mejoraría la función endotelial. Planteamos la hipótesis de que la combinación THIAA-niacina revelaría beneficios no observados con la monoterapia de niacina. En un modelo in vitro, una mezcla de THIAA-niacina inhibió varias citocinas inducidas por el TNF-α en células endoteliales aórticas humanas y en monocitos THP-1; asimismo, esta combinación resultó significativamente más eficaz que la monoterapia de niacina. Posteriormente, en un estudio preliminar de 11 voluntarios con dislipidemia, se estudió el efecto de 125 mg de THIAA y 500 mg de niacina sobre la vasodilatación regulada por el endotelio en respuesta al flujo (VRF). El tratamiento de 12 semanas (2 comprimidos/día) provocó un aumento clínicamente relevante de la VRF, en comparación con la tendencia a la disminución de la VRF observada con el placebo; la diferencia entre grupos fue estadísticamente significativa. Asimismo, el tratamiento con THIAA-niacina mejoró los niveles de colesterol total, de colesterol unido a lipoproteínas de baja densidad y de ácido úrico. No se observaron mejoras significativas de estos parámetros con el placebo. Se detectó un aumento significativo de proteína C reactiva únicamente en el grupo que recibió el placebo. Es posible que los complementos nutricionales y la combinación de THIAA-niacina proporcionen efectos beneficiosos sobre la función endotelial en pacientes con dislipidemia.

A program consisting of a phytonutrient-rich medical food and an elimination diet ameliorated fibromyalgia symptoms and promoted toxic-element detoxification in a pilot trial.

BACKGROUND: An effective treatment for fibromyalgia (FM) has yet to become available. OBJECTIVE: To assess the efficacy ofa lifestyle program consisting of a modified elimination diet and a supplemental medical food on clinical symptoms of FM assessed by the Fibromyalgia Impact Questionnaire (FIQ), FibroQuest Symptoms Survey (FibroQuest), Medical Symptoms Questionnaire (MSQ), metallothionein mRNA expression, and urinary toxic element excretion. METHODS: Eight women (aged 48-74 years) were enrolled in an 8-week pilot trial employing a sequential design. During the initial 4-week Program A (control), participants consumed a modified US Department of Agriculture food pyramid diet and a rice protein powder supplement that provided basic macronutrient support. During the second 4-week Program B (intervention), participants consumed a modified elimination diet and a phytonutrient-rich medical food. RESULTS: Compared to baseline, both programs showed trends toward lower mean FIQ total score, MSQ total score, and FibroQuest total score, FIQ stiffness score, and FibroQuest headaches score. Compared to Program A, Program B resulted in a significant decrease (P< .05) in the FIQpain score and stiffness score. Participants also had better pain tolerance at five tender points during Program B than during Program A. Higher metallothionein mRNA expression was observed during Program B. An increase in creatinine-adjusted mercury excretion and suggestive increase in creatinine-adjusted arsenic excretion were noted when Program B was compared to baseline. Urinary mercury/arsenic concentrations were inversely associated with FIQand FibroQuest scores. CONCLUSIONS: Program B was shown to be a safe and efficacious botanically derived medical food treatment program for the amelioration of FM symptoms.

Nutritional supplementation of hop rho iso-alpha acids, berberine, vitamin D3, and vitamin K1 produces a favorable bone biomarker profile supporting healthy bone metabolism in postmenopausal women with metabolic syndrome.

Metabolic syndrome poses additional risk for postmenopausal women who are already at risk for osteoporosis. We hypothesized that a nutritional supplement containing anti-inflammatory phytochemicals and essential bone nutrients would produce a favorable bone biomarker profile in postmenopausal women with metabolic syndrome. In this 14-week, randomized trial, 51 women were instructed to consume a modified Mediterranean-style, low-glycemic-load diet and to engage in aerobic exercise. Those in the intervention arm (n = 25) additionally received 200 mg hop rho iso-alpha acids, 100 mg berberine sulfate trihydrate, 500 IU vitamin D3, and 500 µg vitamin K1 twice daily. Forty-five women completed the study. Baseline nutrient intake did not differ between arms. Compared with baseline, the intervention arm exhibited an approximate 25% mean decrease (P < .001) in serum osteocalcin (indicative of bone turnover), whereas the placebo arm exhibited a 21% increase (P = .003). Serum 25-hydroxyvitamin D increased 23% (P = .001) in the intervention arm and decreased 12% (P = .03) in the placebo arm. The between-arm differences for osteocalcin and 25-hydroxyvitamin D were statistically significant. Serum insulin-like growth factor I was statistically increased in both arms, but the between-arm differences were not statistically significant. Subanalysis showed that among those in the highest tertile of baseline insulin-like growth factor I, the intervention arm exhibited a significant increase in amino-terminal propeptide of type I collagen, whereas the placebo arm showed a significant decrease at 14 weeks. Treatment with rho iso-alpha acids, berberine, vitamin D3, and vitamin K1 produced a more favorable bone biomarker profile indicative of healthy bone metabolism in postmenopausal women with metabolic syndrome.

Subjects with elevated LDL cholesterol and metabolic syndrome benefit from supplementation with soy protein, phytosterols, hops rho iso-alpha acids, and Acacia nilotica proanthocyanidins.

BACKGROUND: Metabolic syndrome is associated with increased cardiovascular disease (CVD) risk, a risk that is significantly increased when accompanied by elevated low-density lipoprotein cholesterol (LDL-C). Whereas lifestyle therapies are the initial intervention of choice for both of these risk factors, it has not been clearly determined that this approach is efficacious when they occur concomitantly. OBJECTIVE: To evaluate effects of supplementing a lifestyle program with a medical food and nutraceutical in individuals with metabolic syndrome and elevated LDL-C. METHODS: We conducted a subgroup analysis of a 12-week, randomized trial in adults with metabolic syndrome; data from those with LDL-C ≥ 160 mg/dL were analyzed. Control-arm subjects were instructed to consume a modified Mediterranean-style, low-glycemic-load diet (MED, n = 12). Treatment-arm subjects received a phytochemical-enhanced diet (PED, n = 12) consisting of the same low-glycemic-load diet plus a medical food containing soy protein and plant sterols and a nutraceutical containing hops rho iso-alpha acids and acacia proanthocyanidins. All subjects received identical aerobic exercise counseling. RESULTS: At 12 weeks, mean weight loss did not differ between arms. However, the PED arm exhibited greater improvement than the MED arm (P < .05) in total cholesterol, LDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), cholesterol/HDL-C, triglyceride/HDL-C, apolipoprotein (apo) B, apo B/apo A-1, homocysteine, total LDL particle number, and large HDL particle number. All individuals in the PED arm but only one third in the MED arm achieved LDL-C levels < 160 mg/dL. CONCLUSION: Individuals at high CVD risk benefit from a soy/phytosterol containing medical food and phytochemical supplemented lifestyle program.

Hop rho iso-alpha acids, berberine, vitamin D3 and vitamin K1 favorably impact biomarkers of bone turnover in postmenopausal women in a 14-week trial.

Osteoporosis is a major health issue facing postmenopausal women. Increased production of pro-inflammatory cytokines resulting from declining estrogen leads to increased bone resorption. Nutrition can have a positive impact on osteoporosis prevention and amelioration. The objective of this study was to investigate the impact of targeted phytochemicals and nutrients essential for bone health on bone turnover markers in healthy postmenopausal women. In this 14-week, single-blinded, 2-arm placebo-controlled pilot study, all women were instructed to consume a modified Mediterranean-style low-glycemic-load diet and to engage in limited aerobic exercise; 17 randomized to the placebo and 16 to the treatment arm (receiving 200 mg hop rho iso-alpha acids, 100 mg berberine sulfate trihydrate, 500 IU vitamin D(3) and 500 microg vitamin K(1), twice daily). Thirty-two women completed the study. Baseline nutrient intake did not differ between arms. At 14 weeks, the treatment arm exhibited an estimated 31% mean reduction (P = 0.02) in serum osteocalcin (a marker of bone turnover), whereas the placebo arm exhibited a 19% increase (P = 0.03) compared to baseline. Serum 25-hydroxyvitamin D (25(OH)D) increased by 13% (P = 0.24) in the treatment arm and decreased by 25% (P < 0.01) in the placebo arm. The between-arm differences for OC and 25(OH)D were statistically significant. Serum IGF-I was increased in both arms, but the increase was more significant in the treatment arm at 14 weeks (P < 0.01). Treatment with hop rho iso-alpha acids, berberine sulfate trihydrate, vitamin D(3) and vitamin K(1) produced a more favorable bone biomarker profile that supports a healthy bone metabolism.

A science-based, clinically tested dietary approach for the metabolic syndrome.

During the last decade, great strides have been made to delineate the importance of diet in the prevention and treatment of the metabolic syndrome. Dietary recommendations have emphasized a low-fat ("antiatherogenic") diet as the first-line therapeutic approach. However, the complex etiology of the metabolic syndrome would seem to necessitate tailored dietary approaches beyond simple macronutrient modification. Current data have revealed varying biological effects of individual macronutrients within the same category, suggesting that adjusting dietary macronutrient percentages without considering their physiological impact may not be adequate. The concepts of glycemic index and glycemic load support the need for differentiation between various types of carbohydrates. Additionally, significant evidence to date indicates that metabolic syndrome biomarkers improve with dietary patterns rich in phytochemical complexity (e.g., Mediterranean diet). Taking these aspects into account, we designed a specific dietary approach consisting of foods found in the popularized Mediterranean diet, modified to include only those items that are low in glycemic load and grains (gluten) and are antiinflammatory. Initially based on scientific literature, this food plan has since been tested and adapted in our clinic over the past decade. This paper describes the rationale of the dietary program and provides an overview of data on its efficacy in individuals with metabolic syndrome.

Enhancement of a modified Mediterranean-style, low glycemic load diet with specific phytochemicals improves cardiometabolic risk factors in subjects with metabolic syndrome and hypercholesterolemia in a randomized trial.

BACKGROUND: As the worldwide dietary pattern becomes more westernized, the metabolic syndrome is reaching epidemic proportions. Lifestyle modifications including diet and exercise are recommended as first-line intervention for treating metabolic syndrome. Previously, we reported that a modified Mediterranean-style, low glycemic load diet with soy protein and phytosterols had a more favorable impact than the American Heart Association Step 1 diet on cardiovascular disease (CVD) risk factors. Subsequently, we screened for phytochemicals with a history of safe use that were capable of increasing insulin sensitivity through modulation of protein kinases, and identified hops rho iso-alpha acid and acacia proanthocyanidins. The objective of this study was to investigate whether enhancement of a modified Mediterranean-style, low glycemic load diet (MED) with specific phytochemicals (soy protein, phytosterols, rho iso-alpha acids and proanthocyanidins; PED) could improve cardiometabolic risk factors in subjects with metabolic syndrome and hypercholesterolemia. METHODS: Forty-nine subjects with metabolic syndrome and hypercholesterolemia, aged 25-80, entered a randomized, 2-arm, 12-week intervention trial; 23 randomized to the MED arm; 26 to the PED arm. Forty-four subjects completed at least 8 weeks [MED (n = 19); PED (n = 25)]. All subjects were instructed to follow the same aerobic exercise program. Three-day diet diaries and 7-day exercise diaries were assessed at each visit. Fasting blood samples were collected at baseline, 8 and 12 weeks for analysis. RESULTS: Both arms experienced equal weight loss (MED: -5.7 kg; PED: -5.9 kg). However, at 12 weeks, the PED arm experienced greater reductions (P < 0.05) in cholesterol, non-HDL cholesterol, triglycerides (TG), cholesterol/HDL and TG/HDL compared with the MED arm. Only the PED arm experienced increased HDL (P < 0.05) and decreased TG/HDL (P < 0.01), and continued reduction in apo B/apo A-I from 8 to 12 weeks. Furthermore, 43% of PED subjects vs. only 22% of MED subjects had net resolution of metabolic syndrome. The Framingham 10-year CVD risk score decreased by 5.6% in the PED arm (P < 0.01) and 2.9% in the MED arm (P < 0.05). CONCLUSION: These results demonstrate that specific phytochemical supplementation increased the effectiveness of the modified Mediterranean-style low glycemic load dietary program on variables associated with metabolic syndrome and CVD.

Clinical safety and efficacy of NG440: a novel combination of rho iso-alpha acids from hops, rosemary, and oleanolic acid for inflammatory conditions.

In this report, we examine the clinical safety and efficacy of NG440, a phytochemical-based antiinflammatory formula consisting of a combination of rho iso-alpha acids from hops, rosemary, and oleanolic acid. In a previous study, we demonstrated that NG440 significantly decreased pain by 50% in patients with osteoarthritis. Consistent with these data, results from a multicentre trial indicate that NG440 reduced pain scores in patients with joint discomfort, as measured by VAS (visual analog scale) methodology. As demonstrated in an ex vivo clinical study, these effects on pain relief may be due to reduced inflammatory cytokine production including lower prostaglandin E2 formation. Finally, strong data exist to suggest that NG440 is a safe formula for human consumption. Animal toxicity data revealed no adverse effects of NG440 at dosages < or =250 mg.kg-1.day-1 for 21 days. Furthermore, human trial data suggest that NG440 does not negatively impact cardiovascular and gastrointestinal markers normally affected by selective COX-2 enzyme inhibitors, including platelet function, blood pressure, blood cell count, or fecal calprotectin, a measure of gastrointestinal injury. In conclusion, NG440 may serve as a safe and efficacious alternative in some areas where specific COX-2 inhibitors have been traditionally used.